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| summary_text = The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.<ref name="entrez"/>
| summary_text = The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.<ref name="entrez"/>
}}
}}
==Model organisms==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Prkab1'' knockout mouse phenotype
|-
! Characteristic!! Phenotype


|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| [[Recessive]] lethal study || bgcolor="#488ED3"|Normal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open_Field_(animal_test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot_plate_test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#C40000"|Abnormal<ref name="Glucose tolerance test">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAVE/glucose-tolerance-ip/ |title=Glucose tolerance test data for Prkab1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy_X-ray_absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#C40000"|Abnormal<ref name="Clinical chemistry">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAVE/plasma-chemistry/ |title=Clinical chemistry data for Prkab1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Blood plasma|Plasma]] [[immunoglobulin]]s || bgcolor="#C40000"|Abnormal
|-
| [[Haematology]] || bgcolor="#C40000"|Abnormal<ref name="Haematology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAVE/haematology-cbc/ |title=Haematology data for Prkab1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAVE/salmonella-challenge/ |title=''Salmonella'' infection data for Prkab1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| ''[[Citrobacter]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Citrobacter'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MAVE/citrobacter-challenge/ |title=''Citrobacter'' infection data for Prkab1 |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite web |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2010.4142.x/abstract |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |location=''Acta Opthalmologica'' '''88''': 925-7.doi:10.1111/j.1755-3768.2010.4142.x |publisher=Wiley}}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of PRKAB1 function. A conditional [[knockout mouse]] line, called ''Prkab1<sup>tm1a(KOMP)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Prkab1 |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4362414 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{Cite pmid|21677750}}</ref><ref name="mouse_library">{{cite web |url=http://www.nature.com/news/2011/110615/full/474262a.html |title=Mouse library set to be knockout |author=Dolgin E |year=June 2011 |location=''Nature'' '''474''': 262-263. doi:10.1038/474262a}}</ref><ref name="mouse_for_all_reasons">{{cite book |title=A mouse for all reasons |author=Collins FS, Rossant J, Wurst W |year=January 2007 |location=''Cell'' '''128'''(1): 9-13. doi:10.1016/j.cell.2006.12.018 PMID 17218247}}</ref>

Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal| author=van der Weyden L, White JK, Adams DJ, Logan DW| title=The mouse genetics toolkit: revealing function and mechanism. | journal=Genome Biol | year= 2011 | volume= 12 | issue= 6 | pages= 224 | pmid=21722353 | doi=10.1186/gb-2011-12-6-224 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21722353 }} </ref> Twenty five tests were carried out on [[mutant]] mice and five significant abnormalities were observed.<ref name="mgp_reference" /> Homozygous mutant males displayed [[impaired glucose tolerance]]. Animals of both sex had increased circulating [[bilirubin]] levels, increased IgG3 levels, and a number of atypical [[haematology]] parameters.<ref name="mgp_reference" />
==Interactions==
==Interactions==
PRKAB1 has been shown to [[Protein-protein interaction|interact]] with [[PRKAG2]]<ref name=pmid10698692>{{cite journal |last=Cheung |first=P C |authorlink= |coauthors=Salt I P, Davies S P, Hardie D G, Carling D |year=[[2000]]|month=Mar. |title=Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding |journal=Biochem. J. |volume=346 Pt 3 |issue= 3|pages=659–69 |publisher= |location = ENGLAND| issn = 0264-6021| pmid = 10698692 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=1220898 | doi=10.1042/0264-6021:3460659}}</ref> and [[PRKAG1]].<ref name=pmid10698692/>
PRKAB1 has been shown to [[Protein-protein interaction|interact]] with [[PRKAG2]]<ref name=pmid10698692>{{cite journal |last=Cheung |first=P C |authorlink= |coauthors=Salt I P, Davies S P, Hardie D G, Carling D |year=[[2000]]|month=Mar. |title=Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding |journal=Biochem. J. |volume=346 Pt 3 |issue= 3|pages=659–69 |publisher= |location = ENGLAND| issn = 0264-6021| pmid = 10698692 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = |pmc=1220898 | doi=10.1042/0264-6021:3460659}}</ref> and [[PRKAG1]].<ref name=pmid10698692/>
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{{refend}}
{{refend}}
{{PDB Gallery|geneid=5564}}
{{PDB Gallery|geneid=5564}}
[[Category:Genes mutated in mice]]

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Revision as of 17:30, 12 February 2012

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AMPKBI
Identifiers
SymbolAMPKBI
PfamPF04739
InterProIPR006828
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.[1][2]

Template:PBB Summary

Model organisms

Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)Wtsi[10][11] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and five significant abnormalities were observed.[8] Homozygous mutant males displayed impaired glucose tolerance. Animals of both sex had increased circulating bilirubin levels, increased IgG3 levels, and a number of atypical haematology parameters.[8]

Interactions

PRKAB1 has been shown to interact with PRKAG2[16] and PRKAG1.[16]

The 5'-AMP-activated protein kinase beta subunit interaction domain (AMPKBI) is a conserved domain found in the beta subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1, Sip2 and Gal83, which are found in the SNF1 kinase complex.[17] This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known.[18]

References

  1. ^ Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE (1996). "Mammalian AMP-activated protein kinase subfamily". J Biol Chem. 271 (2): 611–4. doi:10.1074/jbc.271.2.611. PMID 8557660. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  2. ^ "Entrez Gene: PRKAB1 protein kinase, AMP-activated, beta 1 non-catalytic subunit".
  3. ^ "Glucose tolerance test data for Prkab1". Wellcome Trust Sanger Institute.
  4. ^ "Clinical chemistry data for Prkab1". Wellcome Trust Sanger Institute.
  5. ^ "Haematology data for Prkab1". Wellcome Trust Sanger Institute.
  6. ^ "Salmonella infection data for Prkab1". Wellcome Trust Sanger Institute.
  7. ^ "Citrobacter infection data for Prkab1". Wellcome Trust Sanger Institute.
  8. ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley.{{cite web}}: CS1 maint: location (link)
  9. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ^ "International Knockout Mouse Consortium".
  11. ^ "Mouse Genome Informatics".
  12. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21677750, please use {{cite journal}} with |pmid=21677750 instead.
  13. ^ Dolgin E (June 2011). "Mouse library set to be knockout". Nature 474: 262-263. doi:10.1038/474262a.{{cite web}}: CS1 maint: location (link)
  14. ^ Collins FS, Rossant J, Wurst W (January 2007). A mouse for all reasons. Cell 128(1): 9-13. doi:10.1016/j.cell.2006.12.018 PMID 17218247.{{cite book}}: CS1 maint: location (link) CS1 maint: location missing publisher (link) CS1 maint: multiple names: authors list (link)
  15. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMID 21722353.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  16. ^ a b Cheung, P C (2000). "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. 346 Pt 3 (3). ENGLAND: 659–69. doi:10.1042/0264-6021:3460659. ISSN 0264-6021. PMC 1220898. PMID 10698692. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  17. ^ Gao G, Fernandez CS, Stapleton D, Auster AS, Widmer J, Dyck JR, Kemp BE, Witters LA (1996). "Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated protein kinase". J. Biol. Chem. 271 (15): 8675–81. doi:10.1074/jbc.271.15.8675. PMID 8621499. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  18. ^ Yang X, Jiang R, Carlson M (1994). "A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex". EMBO J. 13 (24): 5878–86. PMC 395563. PMID 7813428. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

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This article incorporates text from the public domain Pfam and InterPro: IPR006828
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